During the past year, our investigations have proceeded toward studying the effect of immunostimulating agents (C. parvum (CP)) on parenchymal cell regeneration. Continuing investigations have demonstrated that when CP was given 24 hours after partial hepatectomy (PH) when DNA synthesis is at a maximum, percent regeneration, 3HT uptake and total DNA were all increased at 7 and 14 days following PH. Experiments were carried out to explore the beneficial effects of CP on liver regeneration in cirrhotic rats. When CP was given to cirrhotic rats immediately following PH, by 48 hours there was a greater increase in 3HT uptake by cirrhotic animals receiving CP. At 7 days there was an increase in percent regeneration (weight), DNA and 3HT uptake. When repeated doses of CP were given to non-cirrhotic animals liver weight rapidly increased following a first CP injection, more slowly after the second injection and only slightly after the third. 3HT uptake sharply rose after the first injection with an almost equally rapid drop-off. The second injection produced a second increase which was less than that following the initial injection. A similar pattern occurred after the third CP injection. The peak of 3HT uptake was 4-5 days after the first inoculation of CP, it was 2 days after the second or third injections. Additional studies were carried out to ascertain dose response to CP. During the coming year we shall work toward evaluating the effects on liver generation and regeneration of other non-specific stimulating agents purported to have different modes of action, e.g., BCG, Tilorone, Levamisole, Bru-Pel and Glucan. Additional experiments to be done are (a) to confirm and expand on investigations relative to the role of the lymphocyte in hepatic regeneration, (b) the effect of C. parvum on regeneration of the radiated liver, (c) the effect of RES stimulating agents on the cirrhotic liver relative to its repair, (d) the protective effect of CP during or after exposure to hepatotoxic agents, and (e) to determine whether CP permits liver regeneration to take place when given with inhibitory agents such as cytotoxic chemotherapy.